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Drug Interactions Lansoprazole is metabolized through the cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P450 system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various cytochrome P450 isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels. Text Continues Below
In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time. Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin. In a single-dose crossover study examining lansoprazole 30 mg and omeprazole 20 mg each administered alone and concomitantly with sucralfate 1 gram, absorption of the proton pump inhibitors was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with PREVACID Delayed-Release Capsules; this did not interfere with its effect. PREVACID Lansoprazole causes a profound and long-lasting inhibition of gastric acid secretion; therefore, it is theoretically possible that lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e. g., ketoconazole, ampicillin esters, iron salts, digoxin). Carcinogenesis, Mutagenesis, Impairment of Fertility In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated orally with doses of 5 to 150 mg/ kg/ day, about 1 to 40 times the exposure on a body surface (mg/ m 2 ) basis, of a 50-kg person of average height (1. 46 m 2 body surface area) given the recommended human dose of 30 mg/ day (22. 2 mg/ m 2 ). Lansoprazole produced dose-related gastric enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids in both male and female rats. It also increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes. In male rats, lansoprazole produced a dose-related increase of testicular interstitial cell adenomas. The incidence of these adenomas in rats receiving doses of 15 to 150 mg/ kg/ day (4 to 40 times the recommended human dose based on body surface area) exceeded the low background incidence (range = 1. 4 to 10%) for this strain of rat. Testicular interstitial cell adenoma also occurred in 1 of 30 rats treated with 50 mg/ kg/ day (13 times the recommended human dose based on body surface area) in a 1-year toxicity study. In a 24-month carcinogenicity study, CD-1 mice were treated orally with doses of 15 to 600 mg/ kg/ day, 2 to 80 times the recommended human dose based on body surface area. Lansoprazole produced a dose-related increased incidence of gastric ECL cell hyperplasia. It also produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor incidences in male mice treated with 300 and 600 mg/ kg/ day (40 to 80 times the recommended human dose based on body surface area) and female mice treated with 150 to 600 mg/ kg/ day (20 to 80 times the recommended human dose based on body surface area) exceeded the ranges of background incidences in historical controls for this strain of mice. Lansoprazole treatment produced adenoma of rete testis in male mice
receiving 75 to 600 mg/ kg/ day (10 to 80 times the recommended human dose based on body surface area). Lansoprazole was not genotoxic in the Ames test, the ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) test, the in vivo mouse micronucleus test or the rat bone marrow cell chromosomal aberration test. It was positive in in vitro human lymphocyte chromosomal aberration assays. Lansoprazole at oral doses up to 150 mg/ kg/ day (40 times the recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats. Pregnancy Teratogenic Effects. Pregnancy Category B Lansoprazole Teratology studies have been performed in pregnant rats at oral doses up to 150 mg/ kg/ day (40 times the recommended human dose based on body surface area) and pregnant rabbits at oral doses up to 30 mg/ kg/ day (16 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. PREVACID Pregnancy Category C Clarithromycin See WARNINGS (above) and full prescribing information for clarithromycin before using in pregnant women. Nursing Mothers Lansoprazole or its metabolites are excreted in the milk of rats. It is not known whether lansoprazole is excreted in human milk. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from lansoprazole, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and effectiveness of PREVACID have been established in the age group 1 year to 11 years for short-term treatment of symptomatic GERD and erosive esophagitis. Safety and effectiveness have not been established in patients < 1 year or 12-17 years of age. Use of PREVACID in the age group 1 year to 11 years is supported by evidence from adequate and well controlled studies of PREVACID in adults with additional clinical, pharmacokinetic, pharmacodynamic, and safety studies performed in pediatric patients. In an uncontrolled, open-label, U. S. multicenter study, 66 pediatric patients (1 to 11 years of age) with GERD were assigned, based on body weight, to receive an initial dose of either PREVACID 15 mg q. d. if < 30 kg or PREVACID 30 mg q. d. if > 30 kg administered for 8 to 12 weeks. The PREVACID dose was increased (up to 30 mg b. i. d.) in 24 of 66 pediatric patients after 2 or more weeks of treatment if they remained symptomatic. At baseline 85% of patients had mild to moderate overall GERD symptoms (assessed by investigator interview), 58% had non-erosive GERD and 42% had erosive esophagitis (assessed by endoscopy). After 8 to 12 weeks of PREVACID treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of GERD symptoms. Twenty-one of 27 erosive esophagitis patients were healed at 8 weeks and 100% of patients were healed at 12 weeks by endoscopy. GERD Final Visit a % (n/ N) Symptomatic GERD
Improvement in Overall GERD Symptoms b 76% (47/ 62 c ) Erosive Esophagitis
Improvement in Overall GERD Symptoms b Healing Rate 81% (22/ 27) 100% (27/ 27)
a At Week 8 or Week 12
b Symptoms assessed by patients diary kept by caregiver.
c No data were available for 4 pediatric patients. In a study of 66 pediatric patients in the age group 1 year to 11 years old after treatment with PREVACID given orally in doses of 15 mg q. d. to 30 mg b. i. d., increases in serum gastrin levels were similar to those observed in adult studies. Median fasting serum gastrin levels increased 89% from 51 pg/ ml at baseline to 97 pg/ ml [interquartile range (25 th -75 th percentile) of 71-130 pg/ ml] at the final visit. The pediatric safety of PREVACID Delayed-Release Capsules has been ssessed in 66 pediatric patients aged 1 to 11 years of age. Of the 66 patients with GERD 85% (56/ 66) took lansoprazole for 8 weeks and 15% (10/ 66) took it for 12 weeks. The adverse event profile in these pediatric patients resembled that of adults taking lansoprazole. The most frequently reported (2 or more patients) treatment-related adverse events in patients 1 to 11 years of age (N= 66) were constipation (5%) and headache (3%). There were no adverse events reported in this U. S. clinical study that were not previously observed in adults. Use in Women Over 4, 000 women were treated with lansoprazole. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse events were also similar to those seen in males. Use in Geriatric Patients Ulcer healing rates in elderly patients are similar to those in a younger age group. The incidence rates of adverse events and laboratory test abnormalities are also similar to those seen in younger patients. For elderly patients, dosage and administration of lansoprazole need not be altered for a particular indication. Drug Interactions Lansoprazole is metabolized through the cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P450 system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various cytochrome P450 isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels. In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time. Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin. In a single-dose crossover study examining lansoprazole 30 mg and omeprazole 20 mg each administered alone and concomitantly with sucralfate 1 gram, absorption of the proton pump inhibitors was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with PREVACID Delayed-Release Capsules; this did not interfere with its effect. PREVACID Lansoprazole causes a profound and long-lasting inhibition of gastric acid secretion; therefore, it is theoretically possible that lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e. g., ketoconazole, ampicillin esters, iron salts, digoxin). Carcinogenesis, Mutagenesis, Impairment of Fertility In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated orally with doses of 5 to 150 mg/ kg/ day, about 1 to 40 times the exposure on a body surface (mg/ m 2 ) basis, of a 50-kg person of average height (1. 46 m 2 body surface area) given the recommended human dose of 30 mg/ day (22. 2 mg/ m 2 ). Lansoprazole produced dose-related gastric enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids in both male and female rats. It also increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes. In male rats, lansoprazole produced a dose-related increase of testicular interstitial cell adenomas. The incidence of these adenomas in rats receiving doses of 15 to 150 mg/ kg/ day (4 to 40 times the recommended human dose based on body surface area) exceeded the low background incidence (range = 1. 4 to 10%) for this strain of rat. Testicular interstitial cell adenoma also occurred in 1 of 30 rats treated with 50 mg/ kg/ day (13 times the recommended human dose based on body surface area) in a 1-year toxicity study. In a 24-month carcinogenicity study, CD-1 mice were treated orally with doses of 15 to 600 mg/ kg/ day, 2 to 80 times the recommended human dose based on body surface area. Lansoprazole produced a dose-related increased incidence of gastric ECL cell hyperplasia. It also produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor incidences in male mice treated with 300 and 600 mg/ kg/ day (40 to 80 times the recommended human dose based on body surface area) and female mice treated with 150 to 600 mg/ kg/ day (20 to 80 times the recommended human dose based on body surface area) exceeded the ranges of background incidences in historical controls for this strain of mice. Lansoprazole treatment produced adenoma of rete testis in male mice receiving 75 to 600 mg/ kg/ day (10 to 80 times the recommended human dose based on body surface area). Lansoprazole was not genotoxic in the Ames test, the ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) test, the in vivo mouse micronucleus test or the rat bone marrow cell chromosomal aberration test. It was positive in in vitro human lymphocyte chromosomal aberration assays. Lansoprazole at oral doses up to 150 mg/ kg/ day (40 times the recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats. Pregnancy Teratogenic Effects Pregnancy Category B Lansoprazole Teratology studies have been performed in pregnant rats at oral doses up to 150 mg/ kg/ day (40 times the recommended human dose based on body surface area) and pregnant rabbits at oral doses up to 30 mg/ kg/ day (16 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Pregnancy Category C Clarithromycin See WARNINGS (above) and full prescribing information for clarithromycin before using in pregnant women. Nursing Mothers Lansoprazole or its metabolites are excreted in the milk of rats. It is not known whether lansoprazole is excreted in human milk. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from lansoprazole, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. The safety and effectiveness of PREVACID have been established in the age group 1 year to 11 years for short-term treatment of symptomatic GERD and erosive esophagitis. Safety and effectiveness have not been established in patients < 1 year or 12-17 years of age. Use of PREVACID in the age group 1 year to 11 years is supported by evidence from adequate and well controlled studies of PREVACID in adults with additional clinical, pharmacokinetic, pharmacodynamic, and safety studies performed in pediatric patients. In an uncontrolled, open-label, U. S. multicenter study, 66 pediatric patients (1 to 11 years of age) with GERD were assigned, based on body weight, to receive an initial dose of either PREVACID 15 mg q. d. if < 30 kg or PREVACID 30 mg q. d. if > 30 kg administered for 8 to 12 weeks. The PREVACID dose was increased (up to 30 mg b. i. d.) in 24 of 66 pediatric patients after 2 or more weeks of treatment if they remained symptomatic. At baseline 85% of patients had mild to moderate overall GERD symptoms (assessed by investigator interview), 58% had non-erosive GERD and 42% had erosive esophagitis (assessed by endoscopy). After 8 to 12 weeks of PREVACID treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of GERD symptoms. Twenty-one of 27 erosive esophagitis patients were healed at 8 weeks and 100% of patients were healed at 12 weeks by endoscopy. GERD Final Visit a % (n/ N) Symptomatic GERD
Improvement in Overall GERD Symptoms b 76% (47/ 62 c ) Erosive Esophagitis
Improvement in Overall GERD Symptoms b Healing Rate 81% (22/ 27) 100% (27/ 27)
a At Week 8 or Week 12
b Symptoms assessed by patients diary kept by caregiver.
c No data were available for 4 pediatric patients. In a study of 66 pediatric patients in the age group 1 year to 11 years old after treatment with PREVACID given orally in doses of 15 mg q. d. to 30 mg b. i. d., increases in serum gastrin levels were similar to those observed in adult studies. Median fasting serum gastrin levels increased 89% from 51 pg/ ml at baseline to 97 pg/ ml [interquartile range (25 th -75 th percentile) of 71-130 pg/ ml] at the final visit. The pediatric safety of PREVACID Delayed-Release Capsules has been assessed in 66 pediatric patients aged 1 to 11 years of age. Of the 66 patients with GERD 85% (56/ 66) took lansoprazole for 8 weeks and 15% (10/ 66) took it for 12 weeks. The adverse event profile in these pediatric patients resembled that of adults taking lansoprazole. The most frequently reported (2 or more patients) treatment-related adverse events in patients 1 to 11 years of age (N= 66) were constipation (5%) and headache (3%). There were no adverse events reported in this U. S. clinical study that were not previously observed in adults. Use in Women Over 4, 000 women were treated with lansoprazole. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse events were also similar to those seen in males. Use in Geriatric Patients Ulcer healing rates in elderly patients are similar to those in a younger age group. The incidence rates of adverse events and laboratory test abnormalities are also similar to those seen in younger patients. For elderly patients, dosage and administration of lansoprazole need not be altered for a particular indication. Page: << Prev | 1 | 2 | 3 | 4 | 5
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